Streptomycin 2-hydroxy-4-amino benzoate



Patented July 21, 1953 UNITED 1 1 STATE STREPTOMYCIN Z-HYDKOXY -4-AIVII NO BENZOATE 1 Bay A. Patelski, Manhasset, N. Y., and Peter P.

Regna, West New York, N. J assignors' to Chas. Pfizer & 00., Inc., a corporation of Delaware,

' a No Drawing. Application May 14, 1949,

7 Serial No. 93,424 2 Claims..- (01. 260-'-210) peutically useful .salts of streptomycin. More particularly, this invention relates to 2-hydroxyl-aminobenzoi-c acid salts of streptomycin.

It is known'that streptomycin is obtained. from elaboration products formed during'thexgrowth of the microorganism Actznomyces, griseus in a sulfate or the helianthate and then converted to the mineralacid salt.

It is further known that streptomycin is an effective agent in the treatment of tuberculosis. However, it has also been found that the causative organisms of, tuberculosis in some instances become resistant to streptomycin therapy. This has led to a sear-ch for a more eiiective anti- Y mycin salt by dissolving the streptomycin sulfate This 'mvenaoa relates to certain novel theraf h b m lt of 2-hydroxy-4-amin enzoic acid, it is preferred to prepare the desired streptoin water, adding tothe solution the calculated quantity of 2-hydroxy-4-aminobenzoi-c acid, and then precipitating the sulfate by the addition of an aqueous solution of barium hydroxide. The

barium sulfate formed is filtered, and the 2- hydroxyl aminobenzoic acid salt of. streptomycin is recovered from the filtrate. f The invention is further illustrated by, the

lowing example:

' Example Five grams of streptomycin sulfate are dissolved in 50 ml. of water. To this solution are added 3.1 grams of 2-hydroxy-4-aminobenzoic acid. With good agitation, about 18 ml. of wabiotic, but so far as is known none has been ,dis-

covered, although somewhat improved results have been obtained by the addition of certain compounds to penicillin salts.

An object of this invention is to provide new antibiotic salts of improved effectiveness in the treatment of tuberculosis. A further object is I to prepare a novel therapeutically active salt of streptomycin. Further objects will appear hereinafter.

therapeutic properties superior, particularly for tuberculosis therapy, to any heretofore known soluble in water.

be understood that this invention is not limited salts of streptomycin. The2-hydroxy l-amino- 4 benzoic acid is also commonly known as p-aminosalicylic acid.

. In one method for preparing the 2-hydroxy-4- aminobenzoic acid salt of streptomycin according to the present invention, a streptomycin salt, such as streptomycin sulfate in aqueous solution, is reacted with a water-soluble or partially watersoluble salt of 2-hydroxy'4-aminobenzoic acid, for example the barium salt in aqueous solution.

This reaction may be indicated by the following equation:

Because of the relatively poor water solubility tercontaining 1.77 grams of anhydrousbarium hydroxide are slowly added. The precipitated, barium sulfate is removed byfiltration, the pH The 2-hydroxy-4-aminoben'zoic acid salts of streptomycin are white crystalline compounds They are extremely useful antibiotics and have-shown an unusual degree of effectiveness against the tubercle bacilli. This invention combines for the first time in a single compound properties which, so far as is known, have never before been possessed by any antibiotic.

As many apparently widely different embodiments of this invention may be made without departing from the spirit and scope hereof, it is to to the. specific embodiments hereof, except as de-' fined in the appended claims.

We claim: r

'1. 2-hydroxy-4-aminobenzoic acid salts of References Cited in the file of this patent Ratcliff, Readers Digest, November 1945, p. 39,

1 page.

Vander Brook et al., J. Biol. Chem, v.

v. 54 (1947), pp.

Youmans et al., J. Bact.,

415-416, 2 paces. 

2. STREPTOMYCIN TRI-(P-AMINOSALICYLATE). 